Quaternary fluorinated ammonium salts

ABSTRACT

The disclosed quaternary ammonium salts contain a hydrofluoroalkyl substituent on the quaternary nitrogen atom. Processes for the preparation of these salts and compositions containing them are described. These salts and their compositions are active antimicrobial agents.

Unite States Patent Robertson [4 1 Aug. 1, 1972 [54] QUATERNARYFLUORINATED [56] References Cited AMMONIUM SALTS UNITED STATES PATENTS[72] Inventor: Jerry E. Robertson, North Oaks,

Minn. 2,581,336 1/1952 Hartmann et a] ..260/567.6 M

[73] Assignee: Minnesota Mining and Manufactur- Primary Examiner-LeonZltver mg F samt Paul Assistant Examiner-Michael W. Glynn Flledi April13, 1970 Att0rneyKinney, Alexander, Sell, Steldt & Delahunt [21] Al.No.: 27 976 pp 57 ABSTRACT [52] US. Cl....260/501.15, 260/567 6 M,260/570,? The disclosed quaternary ammonium salts contain a 424/329 2523 57 hydrofluoroalkyl substituent on the quaternary [51] Int. Cl ..C07c87/30 n t g t m. r s s f th pr paration f these [58] Field ofSearch....260/567.6 M, 567.6 R, 501.15 salts and compositions containingthem are described.

These salts and their compositions are active antimicrobial agents.

8 Claims, No Drawings QUATERNARY FLUORINATED AMMONIUM SALTS FIELD OF THEINVENTION pounds and compositions containing them are activeantimicrobial agents.

DESCRIPTION OF THE PRIOR ART Many quaternary ammonium salts are known,and some are active antimicrobial compounds. An example of a knownantimicrobial compound of this type is:

wherein X is halogen. See U. S. Pat. No. 2,581,336. When prior artquaternary ammonium salts of this type are dissolved in a suitableliquid carrier and used as disinfectants for bandages or instruments orused in similar in vitro applications, the antimicrobial solution doesnot penetrate well into crevices, holes, cracks and other tiny spaces inthe bandage, surgical instrument, or other item to be disinfected. Thispoor physical penetration of the surface to be disinfected is apparentlydue to the surface tension of the carrier or solvent for theantimicrobial compound.

It is known that quaternary ammonium salts having a fluorocarbontail-containing substituent on the quaternary nitrogen have utility assurface active agents, due to the hydrophobic and oleophobic propertiesof the tail. See, for example, U. S. Pat. No. 2,759,019, issued Aug. 14,1956. So far as the applicant is aware, however, compounds similar tothose of the US. Pat. No. 2,759,0l9, have notbeen tested forantimicrobial activity. More importantly, the fiuoroor perfluorododecylanalogues of the compounds disclosed in U. S. Pat. No. 2,581,336, arenot known per se and, a fortiori, have not been tested for antimicrobialactivity.

Accordingly, this invention contemplates providing chemical compoundswhich combine both surface tension lowering and antimicrobialproperties.

SUMMARY OF THE INVENTION This invention relates to quaternary ammoniumsalts containing four aliphatic substituents bonded to the nitrogenatom, and their novel and useful properties as antimicrobial agents.These compounds have the formula Formula I wherein A is apharmaceutically acceptable anion; Y is hydrogen, halogen or atrifluoromethyl radical which is substituted ortho, meta, or para to X,preferably ortho or para; X is a methylene, ethylene or oxyethyleneradical; and R, is a straight or branched chain perfluoroalkyl radicalof four to carbon atoms or an omegahydro-perfluoroalkyl radical of fourto 10 carbon atoms.

It is a surprising feature of this invention that compounds within thepreceding definition of Formula I have both surface tension lowering andantimicrobial activity, as will be described in detail subsequently.Closely analogous compounds, i.e. those wherein R, can have two or morehydrogen substituents, and/or wherein the R; carbon chain is shorterthan four carbons, appear to be inactive when tested by the usual invitro methods for an inhibitory effect on, for example, Bacillussubtilis, Staphylococcus aureus, Escherichia 0 coli, Streptoccocus sp.and Aspergillus niger.

However, the compounds of Formula I do possess antimicrobial activity,as is evidenced by in vitro tests for inhibitory effects on the growthof B. subtilus. It is difficult to account for the difference inbehavior between these two closely related classes of compounds, i.e.the above-defined Formula I compounds and the shorter carbon chainand/or less fluorinated analogues. Apparently, when fluorocarbon chainsare substituted on the nitrogen of a quaternary amine salt, the patternof antimicrobial activity becomes unpredictable. It is a feature of thisinvention that a specific class of fluorocarbon-containing quaternaryamines, i.e. that defined by Formula I, has been discovered whichpossesses the desired surface tension lowering activity and yet retainsthe antimicrobial activity sometimes attributed to quaternary aminesalts.

The antimicrobial activity of the compounds of Formula I has beenestablished by comparisons with standard antimicrobials such aschlorhexidine acetate and cetylpyridinium chloride. For example, when-R,is n- C F and Y is hydrogen, Formula I is active against Streptococcussp. and S. aureus, as well as B. subtilis. When R, is C F Y is hydrogen;X is ethylene or oxyethylene; and A is trifluoromethanesulfonate oriodide; Formula I has a spectrum of activity including E. coli and A.niger, as well as the Bacillus, Streptococcus, and Staphylococcusorganisms already mentioned. In addition, these compounds have excellentsurface tension lowering properties, particularly when compared withknown antimicrobial agents and even with known commercial surfacetension lowering agents.

DETAILED DESCRIPTION OF THE INVENTION This invention relates tocompounds of the formula:

' [YC H,XN(CH --CH R,]*A

Formula I wherein A is a pharmaceutically acceptable anion, e.g. halide,sulfate, trifluoromethanesulfonate, etc.; Y is hydrogen, halogen, ortrifluoromethyl radical; X is a methylene, ethylene or oxyethyleneradical and R, is a straight or branched chain perfluoroalkyl radical offour to 10 carbon atoms or an omegahydro perfluoroalkyl radical of fourto ten carbon atoms. When Y is halogen or a trifluoromethyl radical, itis substituted ortho, meta, or para to X, preferably ortho or para.

Preferred compounds of Formula I are those wherein Y is hydrogen, X isethylene or oxyethylene, and R, is perfluoroalkyl of six to nine carbonatoms.

The compounds of Formula I were tested for in vitro activities using, inessence, the method described by Vincent, J .G. and Vincent, Helen W.,Proc. Soc. Exptl. Biol. Med, 55: 162-164(1953).

Vincent et al., op. cit., describe an agar-plate diffusion methodemploying culture media designed to meet the minimum essentialrequirements for the growth of the various test organisms. Suitablesugar-salts-agar media are described by Davis et al., op. cit., and aregenerally referred to as agar media. For example, an especially usefuldextrose-salts agar medium contains: sodium and potassium bi-phosphate;magnesium, ammonium, and ferrous sulfate; calcium chloride; dextrose;ionagar; and distilled water. This medium is hereinafter referred to asthe DG medium.

The compounds of the invention may be prepared by at least one ofseveral synthetic routes. Synthesis 1) illustrates the reaction of asecondary amine containing one N-methyl substituent with afluoroalkylating agent to form a tertiary amine. The tertiary amine maythen be quaternized using a methylating agent known to the art such asmethyl halides, methyl trifluoromethanesulfonate, dimethyl sulfate andthe like.

Synthesis 1:

B is part of a suitable leaving group such as trifluoromethyl, p-tolyl,and the like, Z is a sub-class of A (as previously defined) which is afragment of a known methylating agent such as bromine iodine, methylsulfate, trifiuoromethanesulfonate and the like, and Y, X and R, are asdefined previously.

Synthesis (2) illustrates a variation of Synthesis (1) wherein atertiary dimethylamine derivative is treated with a fiuoroalkylatingagent. The tertiary dimethylamine compounds are known, or may readily beprepared by methods known to those skilled in the art, such asalkylation of dimethylamine with an aralkyl halide in the presence ofbase.

Synthesis 2:

Y, X, and R, are as defined previously, and A, in this case, wouldordinarily be B50 wherein B is as defined previously; i.e. Compound 111would normally be Compound lIl.

Synthesis (3) illustrates another variation of Synthesis l whereindimethylamine is reacted with a fluoroalkylating agent to form atertiary amine. This tertiary amine is then quaternized by reaction withan aralkyl halide.

Synthesis 3:

(CH )|NH BSOaCHgR; (CH:)1NCH:R; HB

III VIII IX Y, X, R, and B are as defined previously, and Z, in thiscase, is a halogen of atomic number 17, 35 or 53.

In order to obtain compounds of the present invention where A is aspecific pharmaceutically acceptable anion, the salts of this inventionmay be obtained directly, by anion interchange using methods well knownto the art such as anionic exchange column chromatography, selectiveprecipitation in appropriate solvents or neutralization followed byreprecipitation using a selected anion.

As antimicrobial agents, the compounds of this invention may be applieddirectly to the microbes or conventional carriers and diluents may beincorporated with them before application. The choice of carrier ordiluent and the concentration of the active ingredient are determined bythe use of the composition.

Suitable carriers and diluents include ointments, organic solvents (forexample ethanol), water, solid inert materials such as talc, bentonite,kieselguhr, diatomaceous earth and the like. Emulsifying agents may beused with the compounds of this invention. The compounds may also becontained in surgical drapes and the like.

The following examples illustrate the invention, but are not to beregarded as limiting it in any way.

EXAMPLE 1 N-( 1 l -Dihydroperfluoro-n-octyl)-Nmethyl-N( 2- phenoxyethyl)amine (Compound IVa) Equimolar amounts N-methyl-N-(2-phenoxyethy1)amine, a secondary amine of Formula II of Synthesis (1), supra, andl,l-dihydroperfluoro-n-octyltrifluoromethanesulfonate, (see U. S. Pat.No. 3,419,595 to Robert L. Hansen, issued Dec. 31, 1968) apertluoroalkyl sulfonate of Formula 111 of Synthesis (1), supra, werecombined as follows: 22.24 g. (0.147 mole) of the aforementioned Formula11 amine, and 78.2 g. (0.147 mole) of the aforementioned Formula 111sulfonate were added to a mixture of 250 ml. of dry methyl ethyl ketoneover 20 g. (0.145 mole) of finely powdered anhydrous potassiumcarbonate. The mixture was stirred at room temperature for one hour andthen gradually heated up to reflux temperature over a period of an hour.The mixture was then stirred at this temperature for sixteen hours. Thesolid was then filtered from the mixture and discarded. The filtrate wasevaporated in vacuo to yield a high boiling residue which was vacuumdistilled.

Analytically pure N-( l ,1-dihydroperfluoro-n-octyl)-N-methyl-N-(2-phenoxyethy1) amine, a compound of Formula 1V (Synthesis(1)) hereinafter called Compound lV-a, was obtained. The boiling pointof Compound lV-a at 0.18 mm. was found to be C. The elemental analysiswas as follows:

Calculated for C -,H, F NO:C, 38.3; H, 2.6; N, 2.6

Found: C, 38.5; H, 2.6; N, 2.6

EXAMPLE 2 Using the general procedure of Example 1, secondary amines ofFormula ll (hereinafter Compound ll-b, etc.) were combined with diortri-hydroperfluoro compounds of Formula lII (hereinafter Compound III-b,etc.) as follows:

Formula Ill Fonnula ll Dior tri-hydroperfluoro- Secondary Amine alkylSulfonate No. Compound Name No. Compound Name II-b Nmethyl-N-( 4- lll-bl, l -dihydroperchlorobenzyl)aminefluoro-n-pentyltrifluoromethanesulfonate ll-c N-methyl-N-[2-(4-triiluoromethyl Ill-c l, l -dihydroperphenoxy)ethyl]aminefluoro-n-decyltrifluoromethanesulfonate ll-d N-methyl-N-( 2- lll-d l, l,9-trihydroperfluorobenzyl)amine fluoron-nonyltrifluoromethanesulfonatell-e N-methyl-N-( Z-phenlll-e l,l-dihydroperethyl aminefluoro-n-octyltrifluoromethanesulfonate llf N-methyl-N-benzylill-fl,l-dihydroperamine fluoro-n-heptyltrifluoromethanesulfonate Theresulting Formula IV tertiary amines (Compound lV-b, etc.) were asfollows:

No. Name lV-b N-(l l -dihydroperfluoro-n-pentyl)-N-methyl-N-(4-chlorobenzyl)amine lV-c N-(l l -dihydroperfluoro-n-decyD-N-methyl-N-[Z-(4-trifluoromethylphenoxy)ethyl] amine IV-e N-(l ,l-dihydroperfluoro-n-octyl)-N-methyl- N-(2-phenethyl)amine lV-f N-(l l-dihydroperfluoro-n-heptyD-N-methyl- N-benzylamine EXAMPLE 3 N-( l,l-Dihydroperfluoro-n-octyl)-N,N-dimethyl-N-(2- phenoxyethyl)-ammoniumiodide (Compoundl-a,

iodide) 20 grams (0.14 mole) of methyl iodide, grams (0.019 mole) ofCompound IVa (see Example 1), and 250 ml. of ethanol were heated atreflux temperature for 23 hours. The ethanol was evaporated to give anoil which was poured into diethyl ether. The precipitate which formedwas recrystallized from methanol/diethyl ether to yield colorlesscrystals of Compound l-a (iodide), m.p. l45-l47 C.

Analysis:

Calculated for C H F, lNO: C, 32.0; H, 2.5; N, 2.] Found C, 32.1; H,2.6; N, 2.0

EXAMPLE 4 Using the general procedure of Example 3, the tertiary aminesmade according to Example 2 (Compound IV-b, etc.) were reacted withmethylating agents (methyl halides), as follows:

The resulting quarternary amines of this invention (Compound I-b, etc.)were as follows:

Name

N-( l ,I -dihydroperfluoro-n-pentyl)-N,N-

dimethyl-N-(4-chlorobenzyl)am monium iodide N-(l l-dihydroperfluoro-noctyl)-N ,N-

dimethyl-N {Z-phenethyhammonium iodide N -(l -dihydroperfluoro-n-heptyl)-N .N

dimethyI-N-benzylammonium bromide EXAMPLE 5 N-( l l-Dihydroperfluoro-n-octyl )-N,N-dimethyl-N-( 2- phenoxyethyl) ammoniumtrifluoromethane sulfonate (Compound l-a, trifluoromethane sulfonate)Compound lV-a (see Example 1) was converted to a quaternary amine saltin a manner analogous to the procedure of Example 3, except that themethylating agent was methyl trifluoromethanesulfonate instead of amethyl halide. Compound lV-a (15.0 g.; 0.028 mole) was dissolved in 50ml. of absolute diethyl ether and methyl trifluoromethanesulfonate (14.8g.; 0.09 mole) was added to the solution. A slight heat of reaction wasobserved and within two minutes the colorless solid product crystallizedfrom solution. This product was filtered from the mixture, washed withether and dried. The trifluoromethanesulfonate form of compound l-a,m.p. l03-l08 C., was obtained analytically pure by recrystallizing theproduct from methanol-diethyl ether.

EXAMPLE 6 N-( l l -Dihydroperfluoro-n-octyl)-N,N-dimethyl-N-( 2-phenethyl)- ammonium trifluoromethanesulfonate (Compound I-e,trifluoro-methanesulfonate) Dimethyl phenethylamine (3.0 g., 0.02 mole)was dissolved in 25 ml. of methyl ethyl ketone and added dropwise at50-60 to a solution of 21.38 g. of 1,1- dihydroperfluoro-n-octyltrifluoromethanesulfonate (Compound llI-e) in ml. methyl ethyl ketone.Heating (5060) and stirring was continued for two hours. All operationswere carried out in a nitrogen atmosphere. The reaction mixture wasevaporated to one-half of its original volume and 240 ml. diethyl etherwas added. The precipitate was filtered and dissolved in hot ethanol.The pure trifluoromethanesulfonate form of Compound l-e, m.p. l53l55 C.precipitated on addition of diethyl ether.

Analysis.

Calculated for c,,H.,F,,.No s; C, 33.5; H, 2.5 Found C, 33.8; H, 2.5

EXAMPLE 7 In Vitro Assay of Representative Compounds of Formula I The invitro inhibitory effect of Compounds l-a (iodide) and l-etrifluoromethanesulfonate upon B. subtilis was tested substantiallyaccording to the method of Vincent et al., op. cit., and Davis et al.,op. cit. The DG culture medium used for growth of B. subtilis was asfollows:

Potassium hydrogen phosphate Sodium hydrogen phosphate-dihydrate msulfate-hepta hydrate Ammonium sulfate Calcium chloridedihydrate Ferroussulfate-heptahydrate This DG medium was supplemented with amino acids bymelting the medium in a steam bath, adding the amino acid supplement,and cooling the supplemented medium to 42 C. in a water bath. The aminoacid supplement was as follows: 600 mg/liter glutamic acid, 200 mg/litercystine, 800 m.g.lliter asparagine, and 20 m.g./liter disodium salt ofethylenediaminetetracetic acid. Between 10 and 10 cells of B. subtiliswere added per ml. of the DG-amino acid medium, and the resulting mediumwas dispensed, at 10 ml. per dish, into two 9 cm. circular plastic petridishes. After cooling, a 6.5 mm disc of Whatman No. 2 filter paper wasdipped into a 1 percent (by weight) acetone solution of Compound I-a(iodide), allowed to air dry, and laid on the surface of an innoculatedplate. A second 6.5 mm. disc was likewise treated with a 1 percentacetone solution of Compound l-e (trifluoromethane sulfonate) and laidon an innoculated plate after an identical drying step. Tests show thatthe dipping step will cause three to five microliters of solution(containing 30-50 micrograms of compound) to impregnate each disc. Theplates were incubated at 30 C. for 24 hours, and the diameters of thezones of inhibition were measured, the magnitude of the diameter beingan indication of the effectiveness of the inhibition. The diameter ofthe zone of inhibition for Compound l-a (iodide) was 30 mm.; that ofCompound l-e (trifluoromethanesulfonate) was 33 mm.

Compounds I-a (iodide) and I-e (trifluoromethanesulfonate) were alsotested in an analogous manner, using appropriate culture media andincubation periods, for inhibition of the growth of S. aureus,Streptococcus sp., E. coli, and A. niger. Inhibitory zones ranging from10-23 mm., depending on the organism and the test compound, wereobserved.

In overall evaluations of spectrum and effectiveness of in vitroinhibitory activity the compounds of Formula 1 were comparable to cetylpyridinium chloride and chlorhexidine acetate, two standardantimicrobial compounds known to inhibit the growth of at least one ofthe aforementioned microorganisms.

When the following compound:

was tested and compared with standards in exactly the same manner asCompounds I-a and le, no inhibitory effect whatever was observed on anyof the organisms mentioned in this Example. The difference in activitycould not be explained, but was attributed to the ethoxy componentand/or the shorter carbon chain of the fluorocarbon-containingsubstituent.

EXAMPLE 8 The outstanding surface tension lowering properties ofcompounds of the present invention are exemplified by the followingtabulation, which compares a compound of the invention with cetylpyridinium chloride, a well known commercial antimicrobial agent, andAlevaire a brand of tyloxapol, a commercial surface tension loweringagent.

Comparison of Surface Tension Lowering Surface Tension Concen- (in dynesCompound tration m. Temperature Compound la 50 mg. 22 F. (35C.)

/50 ml. (iodide) 28 72F. (22.2C.) Cetyl pyridinium 25 mg. 42 73F.(22.8C.)

/50 ml. chloride 50 mg. 45.5"

I50 ml. Alevaire commercial 40.7 7lF. (2|.7C.) (tyloxapol sample (av. ofcomposition) 3 trials) A standard antimicrobial compound; see Example 7.

"Literature value at 25 C. (77F), 50 mg./ml is 43 dynes/cm. [MerckIndex, 7th Edition, p. 227 I960), Merck Co., Inc.. Rahway. New Jersey.]

The measurements were taken using standard methods with an lnstronUniversal Testing Machine and a DuNuoy ring at a rate of l cm./min.

What is claimed is:

1. A compound of the formula wherein:

A is a pharmaceutically acceptable anion;

Y is selected from the group consisting of hydrogen,

halogen and trifluoromethyl;

X is selected from the group consisting of methylene,

ethylene and oxyethylene; and

R, is selected from the group consisting of perfluoroalkyl radicals offour to 10 carbon atoms and omega-hydro-perfluoroalkyl radicals of fourto 10 carbon atoms.

2. A compound according to claim 1 wherein Y is hydrogen.

3. A compound according to claim 1 wherein R, is a straight chainperfluoroalkyl radical of four to 10 carbon atoms.

4. A compound according to claim 2 wherein X is selected from ethyleneor oxyethylene and R, is a perfluoroalkyl radical of six to nine carbonatoms.

5. A compound according to claim 1 wherein said compound is an N-( l l-dihydroperfluoro-n-octyl)-N,N-dimethyl-N- (2-phenoxyethyl )ammoniumsalt, the anion of said salt being said pharmaceutically acceptableanion.

6. A compound according to claim 5 wherein said anion is iodide.

7. A compound according to claim 1 wherein said compound is an N-( l l-dihydroperfluoro-n-octyl)-N,N-dimethyl-N- (2-phenethyl )ammonium salt,the anion of said salt being said pharmaceutically acceptable anion.

8. A compound according to claim 7 wherein said 5 anion istrifluoromethanesulfonate.

STA PATENT @FMQE QE'HFMA'EE n Patent No. 3, Dated g st 1, 1972Inventor(s) rry E. Robertson It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

Ihe Title should read, as follows: FLUORINATED QUATERNARY AMMONIUM SALTSColumn 1, line 17, delete the "c", so that the first portion of theformula reads, as follows:

Column 2, lines 37- 42, correct type style (remove italics).

The only italicized words in these lines are E coli and A niger 5 line65, change "(1953)" to (19 4 4) and at the end of the line change theperiod to a comma and insert: and Davis and Mingioli, Jour. Bact. 66:29-136 (1953) o Column 5, line 21, after "ethyl" and before "amine"insert a parenthesis and move these words to the right to line up withthe column headed "Compound Name".

Column 7, line &8, insert C before "F" at the end of the line, line &9,insert B after the so the formula will read:

[C H CH CH N(CH -CH CH OCH CF CF H] Bl" line 5 1, delete the hyphen atthe end of the line and insert y to complete ethoxy line 55, delete "y"at the beginning of the line.

Signed and sealed this 13th day of March 1973.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOTTSCHALK Attesting Officer Commissionerof Patents ORM O-I050 (10-69) UNITED STATES PATENT GFFICE CERTIFICATE 0FPatent No. 3, Dated August 1, 1972 Inventor(s) Jerry E. Robertson It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

The Title should read, as follows: FLUORINA'I'ED QUATERNARY AMMONIUMSALTS Column 1, line 17, delete the "0'', so that the first portion ofthe formula reads as follows:

Column 2, lines 37- 42, correct type style (remove italics).

The only italicized words in these lines are E coli and A niger line 65,change "(1953)" to (19 M) and at the end of the line change the periodto a comma and insert: and Davis and Mingioli, Jour. Bact. 66: 129-136(1953) a Column 5, line 21, after "ethyl" and before "amine" insert aparenthesis and move these words to the right to line up with the columnhe aded Compo und Name".

Column 7, line 48, insert C before "F" at the end of the line, line 49,insert B after the so the formula will read:

[C H CH CH N(CH -CH CH OCH CF CF H] BI line 5 delete the hyphen at theend of the line and insert y to complete ethoxy line 55, delete "y" atthe beginning of the line.

Signed and sealed this 13th day of March 1973.

(SEAL) Attest:

EDWARD M.PLETCHER,JR. ROBERT GOTTSCHALK Attesting Officer Commissionerof Patents RM PO-IOSO (IO-69) USCOMM-DC 60376-P69 Us GOVERNMENT PRINTINGOFFICE: I989 0-386-334

2. A compound according to claim 1 wherein Y is hydrogen.
 3. A compoundaccording to claim 1 wherein Rf is a straight chain perfluoroalkylradical of four to 10 carbon atoms.
 4. A compound according to claim 2wherein X is selected from ethylene or oxyethylene and Rf is aperfluoroalkyl radical of six to nine carbon atoms.
 5. A compoundaccording to claim 1 wherein said compound is anN-(1,1-dihydroperfluoro-n-octyl)-N,N-dimethyl-N-(2-phenoxyethyl)ammoniumsalt, the anion of said salt being said pharmaceutically acceptableanion.
 6. A compound according to claim 5 wherein said anion is iodide.7. A compound according to claim 1 wherein said compound is anN-(1,1-dihydroperfluoro-n-octyl)-N,N-dimethyl-N-(2-phenethyl)ammoniumsalt, the anion of said salt being said pharmaceutically acceptableanion.
 8. A compound according to claim 7 wherein said anion istrifluoromethanesulfonate.